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Abstract Aims Clinical trials in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) commonly have detailed eligibility criteria. This may contribute to challenges with efficient enrolment and questions regarding the generalizability of trial findings. Methods and results Patients with HFmrEF/HFpEF from a large US healthcare system were identified through a computable phenotype applied in linked imaging and electronic health record databases. We evaluated shared eligibility criteria from five recent/ongoing HFmrEF/HFpEF trials (PARAGON‐HF, EMPEROR‐Preserved, DELIVER, FINE‐ARTS, and SPIRRIT‐HFpEF) and compared clinical and echocardiographic features as well as outcomes between trial‐eligible and trial‐ineligible patients. Among 5552 patients with HFpEF/HFmrEF, 792 (14%) were eligible for trial consideration, having met all criteria assessed. Causes of ineligibility included lack of recent loop diuretics (37%), significant pulmonary disease (24%), reduced estimated glomerular filtration rate (17%), recent stroke/transient ischaemic attack (13%), or low natriuretic peptides (12%); 53% of ineligible patients had >1 reason for exclusion. Compared with eligible patients, ineligible patients were younger (age 71 vs. 75 years, P

Abstract Clinical evidence generation from and for representative populations can be improved through increased research access and ease of trial participation. To improve access and participation, a modern trial infrastructure is needed that broadens research into more routine practice. This commentary highlights current barriers, areas of advancement, and actions needed to enable continued transformation toward a modern trial infrastructure for an improved evidence generation system. The focus of this commentary is on the development of medical products (e.g., drugs, devices, biologics) and infrastructure issues within the United States, with the aim to have broader, multi-national applicability.

The COVID-19 pandemic and the subsequent measures taken to control its spread had deep impacts on transportation behavior. This paper presents a methodology for evaluating the changes in bike-share use and focuses on the identification of extraordinary trip-making activity seen in Chicago’s Divvy bike-share program prior to and over the course of the COVID-19 pandemic. An analysis period from January 2018 to April 2021 was subdivided into three time periods: pre-pandemic, citywide lockdown, and post-lockdown for all census tracts within the city of Chicago. Over the analysis window defined, an anomaly detection algorithm was used to characterize the nature of bike-share usage where anomalous trips were those that fell outside of the forecasted ranges. The changes in census tract-level bike-share usage were used to interpret how static census tract-level attributes—land use, transit connectivity, demographics, and bike infrastructure—may have contributed to varying responses across the city’s bike-share system. Principal component analysis was used to interpret the relationship between the dynamic trip-making characterizations and the static census tract-level attributes. Census tracts that transitioned from exhibiting below average to above average bike-share trip-making tended to have highly correlated bike infrastructure metrics. On the other hand, census tracts with consistently above average trip-making had highly correlated demographic characteristics, the values of which were consistent with their standing as key communities for service and essential workers. Overall, results indicate that post-lockdown, bike-sharing activity had grown significantly across the entire city, supporting the claim that the pandemic worked to accelerate bicycling uptake in urban areas.

OBJECTIVES:. We aimed to 1) describe patterns of beta-blocker utilization among critically ill patients following moderate–severe traumatic brain injury (TBI) and 2) examine the association of early beta-blocker exposure with functional and clinical outcomes following injury. DESIGN:. Retrospective cohort study. SETTING:. ICUs at 18 level I, U.S. trauma centers in the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. PATIENTS:. Greater than or equal to 17 years enrolled in the TRACK-TBI study with moderate–severe TBI (Glasgow Coma Scale of

Abstract Background We examined multi-dimensional clinical and laboratory data in participants with normoglycemia, prediabetes, and diabetes to identify characteristics of prediabetes and predictors of progression from prediabetes to diabetes or reversion to no diabetes. Methods The Project Baseline Health Study (PBHS) is a multi-site prospective cohort study of 2502 adults that conducted deep clinical phenotyping through imaging, laboratory tests, clinical assessments, medical history, personal devices, and surveys. Participants were classified by diabetes status (diabetes [DM], prediabetes [preDM], or no diabetes [noDM]) at each visit based on glucose, HbA1c, medications, and self-report. Principal component analysis (PCA) was performed to create factors that were compared across groups cross-sectionally using linear models. Logistic regression was used to identify factors associated with progression from preDM to DM and for reversion from preDM to noDM. Results At enrollment, 1605 participants had noDM; 544 had preDM; and 352 had DM. Over 4 years of follow-up, 52 participants with preDM developed DM and 153 participants reverted to noDM. PCA identified 33 factors composed of clusters of clinical variables; these were tested along with eight individual variables identified a priori as being of interest. Six PCA factors and six a priori variables significantly differed between noDM and both preDM and DM after false discovery rate adjustment for multiple comparisons (q

Abstract Nanobiotechnology is one of the leading research areas in biomedical science, developing rapidly worldwide. Among various types of nanoparticles, carbon nanomaterials (CNMs) have attracted a great deal of attention from the scientific community, especially with respect to their prospective application in the field of disease diagnosis and therapy. The unique features of these nanomaterials, including favorable size, high surface area, and electrical, structural, optical, and chemical properties, have provided an excellent opportunity for their utilization in theranostic systems. Carbon nanotubes, carbon quantum dots, graphene, and fullerene are the most employed CNMs in biomedical fields. They have been considered safe and efficient for non‐invasive diagnostic techniques such as fluorescence imaging, magnetic resonance imaging, and biosensors. Various functionalized CNMs exhibit a great capacity to improve cell targeting of anticancer drugs. Due to their thermal properties, they have been extensively used in cancer photothermal and photodynamic therapy assisted by laser irradiation and CNMs. CNMs also can cross the blood‐brain barrier and have the potential to treat various brain disorders, for instance, neurodegenerative diseases, by removing amyloid fibrils. This review has summarized and emphasized on biomedical application of CNMs and their recent advances in diagnosis and therapy.

Abstract The Project Baseline Health Study (PBHS) was launched to map human health through a comprehensive understanding of both the health of an individual and how it relates to the broader population. The study will contribute to the creation of a biomedical information system that accounts for the highly complex interplay of biological, behavioral, environmental, and social systems. The PBHS is a prospective, multicenter, longitudinal cohort study that aims to enroll thousands of participants with diverse backgrounds who are representative of the entire health spectrum. Enrolled participants will be evaluated serially using clinical, molecular, imaging, sensor, self-reported, behavioral, psychological, environmental, and other health-related measurements. An initial deeply phenotyped cohort will inform the development of a large, expanded virtual cohort. The PBHS will contribute to precision health and medicine by integrating state of the art testing, longitudinal monitoring and participant engagement, and by contributing to the development of an improved platform for data sharing and analysis.

Newer data platforms offer increased opportunity to share multidimensional health data with research participants, but the preferences of participants for which data to receive and how is evolving. Our objective is to describe the preferences and expectations of participants for the return of individual research results within Project Baseline Health Study (PBHS). The PBHS is an ongoing, multicenter, longitudinal cohort study with data from four initial enrollment sites. PBHS participants are recruited from the general population along with groups enriched for heart disease and cancer disease risk. Cross-sectional data on return of results were collected in 2017-2018 from an (1) in-person enrollment survey (n = 1,890), (2) benchmark online survey (n = 1,059), and (3) participant interviews (n = 21). The main outcomes included (1) preferences for type of information to be added next to returned results, (2) participant plans for sharing returned results with a non-study clinician, and (3) choice to opt-out of receiving genetic results. Results were compared by sociodemographic characteristics. Enrollment and benchmark survey respondents were 57.1% and 53.5% female, and 60.0% and 66.2% white, respectively. Participants preferred the following data types be added to returned results in the future: genetics (29.9%), heart imaging, (16.4%), study watch (15.8%), and microbiome (13.3%). Older adults (OR 0.60, 95% CI: 0.41-0.87) were less likely to want their genetic results returned next. Forty percent of participants reported that they would not share all returned results with their non-study clinicians. Black (OR 0.64, 95% CI 0.43-0.95) and Asian (OR 0.47, 95% CI 0.30-0.73) participants were less likely, and older participants more likely (OR 1.45-1.61), to plan to share all results with their clinician than their counterparts. At enrollment, 5.8% of participants opted out of receiving their genetics results. The study showed that substantial heterogeneity existed in participant's preferences and expectations for return of results, and variations were related to sociodemographic characteristics.

Background There are conflicting data regarding the benefit of primary prevention implantable cardioverter‐defibrillators (ICDs) in patients with diabetes mellitus and heart failure (HF) with reduced ejection fraction. We aimed to assess the comparative effectiveness of ICD placement in patients with diabetes mellitus and HF with reduced ejection fraction. Methods and Results Data were obtained from the Get With the Guidelines–Health Failure registry, linked with claims from the Centers for Medicare & Medicaid Services. We used a Cox proportional hazards model censored at 5 years with propensity score matching. Of the 17 186 patients with HF with reduced ejection fraction from the Centers for Medicare & Medicaid Services claims database (6540 with diabetes mellitus; 38%), 1677 (646 with diabetes mellitus; 39%) received an ICD during their index HF hospitalization or were prescribed an ICD at discharge. Patients with diabetes mellitus and an ICD (n=646), as compared with those without an ICD (n=1031), were more likely to be younger (74 versus 78 years of age) and have coronary artery disease (68% versus 60%). After propensity matching, ICD use among patients with diabetes mellitus, as compared with those without an ICD, was associated with a reduced risk of all‐cause mortality at 5 years after HF discharge (54% versus 59%; multivariable hazard ratio, 0.73; 95% CI, 0.64–0.82; P

Background We aimed to determine if there is an association between hospital quality and the likelihood of a given hospital being a preferred transfer destination for stroke patients. Methods and Results Data from Medicare claims identified acute ischemic stroke transferred between 394 northeast US hospitals from 2007 to 2011. Hospitals were categorized as transferring (n=136), retaining (n=241), or receiving (n=17) hospitals based on the proportion of acute ischemic stroke encounters transferred or received. We identified all 6409 potential dyads of sending and receiving hospitals, and categorized dyads as connected if ≥5 patients were transferred between the hospitals annually (n=82). We used logistic regression to identify hospital characteristics associated with establishing a connected dyad, exploring the effect of adjusting for different quality measures and outcomes. We also adjusted for driving distance between hospitals, receiving hospital stroke volume, and the number of hospitals in the receiving hospital referral region. The odds of establishing a transfer connection increased when rate of alteplase administration increased at the receiving hospital or decreased at the sending hospital, however this finding did not hold after applying a potential strategy to adjust for clustering. Receiving hospital performance on 90‐day home time was not associated with likelihood of transfer connection. Conclusions Among northeast US hospitals, we found that differences in hospital quality, specifically higher levels of alteplase administration, may be associated with increased likelihood of being a transfer destination. Further research is needed to better understand acute ischemic stroke transfer patterns to optimize stroke transfer systems.

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults with an extremely poor prognosis. There is a dire need to develop effective therapeutics to overcome the intrinsic and acquired resistance of GBM to current therapies. The process of developing novel anti-neoplastic drugs from bench to bedside can incur significant time and cost implications. Drug repurposing may help overcome that obstacle. A wide range of drugs that are already approved for clinical use for the treatment of other diseases have been found to target GBM-associated signaling pathways and are being repurposed for the treatment of GBM. While many of these drugs are undergoing pre-clinical testing, others are in the clinical trial phase. Since GBM stem cells (GSCs) have been found to be a main source of tumor recurrence after surgery, recent studies have also investigated whether repurposed drugs that target these pathways can be used to counteract tumor recurrence. While several repurposed drugs have shown significant efficacy against GBM cell lines, the blood–brain barrier (BBB) can limit the ability of many of these drugs to reach intratumoral therapeutic concentrations. Localized intracranial delivery may help to achieve therapeutic drug concentration at the site of tumor resection while simultaneously minimizing toxicity and side effects. These strategies can be considered while repurposing drugs for GBM.

BackgroundLower care quality and an increase in adverse outcomes as a result of new medical trainees is a concept well rooted in popular belief, termed the “July phenomenon.” Whether this phenomenon occurs in acute ischemic stroke has not been well studied. Methods and ResultsWe analyzed data from patients admitted with ischemic stroke in 1625 hospitals participating in the Get With The Guidelines–Stroke program for the 5‐year period between January 2009 and December 2013. We compared acute stroke treatment processes and in‐hospitals outcomes among the 4 quarters (first quarter: July–September, last quarter: April–June) of the academic year. Multivariable logistic regression models were used to evaluate the relationship between academic year transition and processes measures. A total of 967 891 patients were included in the study. There was a statistically significant, but modest (

Smart mobility is a central issue in the recent discourse about urban development policy towards smart cities. The design of innovative and sustainable mobility infrastructures as well as public policies require cooperation and innovations between various stakeholders—businesses as well as policy makers—of the business ecosystems that emerge around smart city initiatives. This poses a challenge for deploying instruments and approaches for the proactive management of such business ecosystems. In this article, we report on findings from a smart city initiative we have used as a case study to inform the development, implementation, and prototypical deployment of a visual analytic system (VAS). As results of our design science research we present an agile framework to collaboratively collect, aggregate and map data about the ecosystem. The VAS and the agile framework are intended to inform and stimulate knowledge flows between ecosystem stakeholders in order to reflect on viable business and policy strategies. Agile processes and roles to collaboratively manage and adapt business ecosystem models and visualizations are defined. We further introduce basic categories for identifying, assessing and selecting Internet data sources that provide the data for ecosystem models and we detail the ecosystem data and view models developed in our case study. Our model represents a first explication of categories for visualizing business ecosystem models in a smart city mobility context.

Lactobacillus reuteri and Bifidobacterium bifidum were inoculated (2.8·10^8 and 4.7·10^8 CFU/mL, respectively) into reconstituted whey containing sucrose and pectin in order to prepare a fermented probiotic product. Inoculation levels were: 0.5, 1 or 2 % for Lactobacillus reuteri and 0.5 or 1 % for Bifidobacterium bifidum. The treatment with the highest bacterial counts and sensory scores was selected and stored at 4 °C for 30 days. Microbial counts, changes in pH values, titratable acidity and both triangle test and sensory attributes were monitored on the stored product. The beverage fermented for approx. 11 h and prepared with 2 % Lactobacillus reuteri and 0.5 % Bifidobacterium bifidum met the probiotic criterion by maintaining both bacterial populations at counts greater than 10^6 CFU/mL for the whole storage period. Titratable acidity and pH values as well as sensory properties did not change appreciably during the first 14 days of storage. At the end of the storage period (30 days), slight acidification was detected, although the beverage still retained an acceptable flavour.

Mucus hypersecretion by airway epithelium is a hallmark of inflammation in allergic asthma and results in airway narrowing and obstruction. Others have shown that administration a TH2 cytokine, IL-13 is sufficient to cause mucus hypersecretion in vivo and in vitro. Asthma therapy often utilizes β2-adrenoceptor (β2AR) agonists, which are effective acutely as bronchodilators, however chronic use may lead to a worsening of asthma symptoms. In this study, we asked whether β2AR signaling in normal human airway epithelial (NHBE) cells affected mucin production in response to IL-13. This cytokine markedly increased mucin production, but only in the presence of epinephrine. Mucin production was blocked by ICI-118,551, a preferential β2AR antagonist, but not by CGP-20712A, a preferential β1AR antagonist. Constitutive β2AR activity was not sufficient for IL-13 induced mucin production and β-agonist-induced signaling is required. A clinically important long-acting β-agonist, formoterol, was as effective as epinephrine in potentiating IL-13 induced MUC5AC transcription. IL-13 induced mucin production in the presence of epinephrine was significantly reduced by treatment with selective inhibitors of ERK1/2 (FR180204), p38 (SB203580) and JNK (SP600125). Replacement of epinephrine with forskolin + IBMX resulted in a marked increase in mucin production in NHBE cells in response to IL-13, and treatment with the inhibitory cAMP analogue Rp-cAMPS decreased mucin levels induced by epinephrine + IL-13. Our findings suggest that β2AR signaling is required for mucin production in response to IL-13, and that mitogen activated protein kinases and cAMP are necessary for this effect. These data lend support to the notion that β2AR-agonists may contribute to asthma exacerbations by increasing mucin production via activation of β2ARs on epithelial cells.

Annual temperatures in the circumpolar Arctic are rising at 2-3 times the global average, reducing ecologic barriers for arthropod reproduction and fueling shifts in insect diversity and distribution (2,2). The [...]